Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by gait dysfunction in later stages of the disease. PD hallmarks include a decrease in stride length, run speed, and swing time; an increase in stride time, stance time, and base of support; dopaminergic degeneration in the basal ganglia; and cholinergic degeneration in the pedunculopontine nucleus (PPN). A progressive animal model of PD is needed to identify treatments for gait dysfunction. The goal of this study was to quantify progressive gait degeneration in PTEN-induced putative kinase 1 knockout (P1KO) rats and investigate neurodegeneration as potential underlying mechanisms. Gait analysis was performed in male P1KO and wild-type rats at 5 and 8 months of age and immunohistochemical analysis at 8 months. Multiple parameters of volitional gait were measured using a runway system. P1KO rats exhibited significant gait deficits at 5 months, but not 8 months. Gait abnormalities improved over time suggesting compensation during behavioral testing. At 8 months a 15% loss of tyrosine hydroxylase (TH) in the striatum, a 27% loss of TH-positive cells in the substantia nigra pars compacta, and no significant loss of choline acetyltransferase-positive cells in the PPN was found. Dopaminergic cell loss may contribute to gait deficits in the P1KO model, but not cholinergic cell loss. The P1KO rat with the greatest dopamine loss exhibited the most pronounced PD-like gait deficits, highlighting variability within the model. Further analysis is required to determine the suitability of the P1KO rat as a progressive model of gait abnormalities in PD.

中文翻译：

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多巴胺能而非胆碱能神经变性与 PINK1 敲除大鼠的步态障碍相关


帕金森病（PD）是一种进行性神经退行性疾病，其特征是疾病后期的步态功能障碍。 PD 标志包括步幅、跑步速度和摆动时间的减少；增加步幅时间、站立时间和支撑基础；基底神经节的多巴胺能变性；和桥脚核（PPN）的胆碱能变性。需要一种渐进的 PD 动物模型来确定步态功能障碍的治疗方法。本研究的目的是量化 PTEN 诱导的推定激酶 1 敲除 (P1KO) 大鼠的进行性步态退化，并研究神经退化作为潜在的潜在机制。对 5 个月和 8 个月大的雄性 P1KO 和野生型大鼠进行步态分析，并在 8 个月大时进行免疫组织化学分析。使用跑道系统测量了意志步态的多个参数。 P1KO 大鼠在 5 个月时表现出明显的步态缺陷，但在 8 个月时则没有。随着时间的推移，步态异常有所改善，这表明行为测试期间存在补偿。 8 个月时，纹状体中酪氨酸羟化酶 (TH) 损失 15%，黑质致密部 TH 阳性细胞损失 27%，PPN 中胆碱乙酰转移酶阳性细胞没有明显损失。多巴胺能细胞损失可能导致 P1KO 模型中的步态缺陷，但胆碱能细胞损失则不然。多巴胺损失最大的 P1KO 大鼠表现出最明显的 PD 样步态缺陷，凸显了模型内的变异性。需要进一步分析以确定 P1KO 大鼠是否适合作为 PD 步态异常的进展模型。